The long term goal of this project is to determine how odorous substances are detected and identified by humans. This proposal is focussed on the first step in this process, the transduction of odorous stimuli into an electrophysiological response. Olfactory transduction determines the information which is extracted about an odor stimulus and transmitted to the brain. Therefore, elucidating the transduction mechanism is an essential step toward understanding how olfactory information is processed by the brain. Recent studies have suggested the involvement of the intracellular messengers, cyclic AMP (cAMP) and inositol trisphosphate (IP3) in olfactory transduction. To elucidate the roles of cAMP and IP3, as well as possible interactions between them, it will be necessary to provide the following information: 1) the distribution of cAMP and IP3 mechanisms within and among olfactory receptor cells, 2) the contributions of cAMP and IP3 to odorant-induced currents, 3) the odorant specificities of the cAMP and IP3 mechanisms, and 4) the mechanisms by which cAMP and IP3 levels are regulated. The experiments proposed here will utilize conventional patch clamp recordings from single cells, combined with two novel recording methods which are essential to providing the information described above. These results will determine the roles of cAMP and IP3 in olfactory transduction. In addition, evidence will be provided concerning alternate transduction mechanisms. Because olfactory transduction occurs in the olfactory receptor cilia which are exposed to the external environment, the transduction mechanism may be particularly vulnerable to the effects of toxic substances and infection. Indeed, olfactory deficits are correlated with several neurological diseases. Consequently, knowledge of the transduction mechanism may aid in elucidating the etiologies of olfactory and other neurological disorders.